Clear Cell Renal Cell Carcinoma
Conditions
Keywords
Clear Cell Renal Cell Carcinoma, Neoadjuvant Therapy, PD-L1, Anlotinib, Nephron-Sparing Surgery
Brief summary
This is a prospective, multicenter, single-arm phase II study evaluating the efficacy and safety of neoadjuvant PD-L1 inhibitor TQB2450 in combination with anlotinib in patients with locally advanced, high-complexity (RENAL score ≥10) clear cell renal cell carcinoma (ccRCC). The primary objective is to determine whether neoadjuvant therapy can increase the rate of successful nephron-sparing surgery. In addition, this study incorporates a pre-specified translational research platform including circulating tumor DNA (ctDNA) methylation-based minimal residual disease (MRD) monitoring, tumor multi-omics profiling, and radiomics analysis. Artificial intelligence-based models will be developed to predict treatment response and surgical conversion, enabling precision neoadjuvant strategies.
Detailed description
Patients with anatomically high-complexity locally advanced ccRCC (RENAL score ≥10) often require radical nephrectomy or technically challenging partial nephrectomy, resulting in increased perioperative risks and long-term renal function impairment. Evidence supporting neoadjuvant strategies in this specific high-complexity population remains limited. This study evaluates a novel neoadjuvant approach combining PD-L1 blockade (TQB2450) with the multi-target tyrosine kinase inhibitor anlotinib. PD-L1 inhibition restores anti-tumor immunity, while antiangiogenic therapy promotes vascular normalization and enhances immune cell infiltration. This dual mechanism may improve tumor shrinkage and facilitate surgical conversion, particularly in central or hilar tumors. Patients will receive 2-4 cycles of neoadjuvant therapy, followed by imaging assessment and multidisciplinary team (MDT) evaluation. Surgery will be performed within a predefined window after treatment completion. A key translational component includes longitudinal ctDNA methylation-based MRD monitoring at four time points (baseline, after 2 cycles, pre-surgery, and post-surgery), combined with tumor tissue RNA expression and DNA methylation profiling, as well as radiomics feature extraction. These data will be integrated using machine learning algorithms to construct predictive models for treatment response and nephron-sparing surgery feasibility.
Interventions
DRUGTQB2450 + Anlotinib
Drug: TQB2450 (PD-L1 inhibitor) 1200 mg intravenously every 3 weeks Drug: Anlotinib 12 mg orally once daily (2 weeks on, 1 week off) Treatment duration: 2-4 cycles prior to surgery
Sponsors
RenJi Hospital
Huadong Hospital
Chinese PLA General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a prospective, multicenter, single-arm phase II study evaluating the efficacy and safety of neoadjuvant PD-L1 inhibitor TQB2450 in combination with anlotinib in patients with locally advanced, high-complexity (RENAL score ≥10) clear cell renal cell carcinoma (ccRCC).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* • Age ≥18 years * ECOG performance status 0-2 * Histologically confirmed clear cell renal cell carcinoma * Clinical stage cT2-T3aN0M0 (AJCC 8th edition) * RENAL nephrometry score ≥10 * Tumor assessed as requiring radical nephrectomy or complex partial nephrectomy * Adequate organ function * Signed informed consent
Exclusion criteria
* • Prior systemic therapy for RCC (including ICIs or TKIs) * Non-clear cell histology or sarcomatoid/rhabdoid differentiation \>20% * Active autoimmune disease requiring systemic therapy * Active uncontrolled infection (HBV/HCV/HIV) * Prior organ transplantation * Uncontrolled cardiovascular or pulmonary disease * Pregnancy or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Successful Nephron-Sparing Surgery | At the time of surgery | Defined as the proportion of patients who undergo partial nephrectomy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MDT-Defined Conversion to Nephron-Sparing Surgery | Pre-surgery | o Defined as conversion from pre-treatment planned radical nephrectomy or complex partial nephrectomy to post-treatment feasibility of standard or simplified partial nephrectomy；o Determined by a centrally reviewed multidisciplinary team based on imaging |
| Objective Response Rate (ORR) | Pre-surgery | Assessed by RECIST v1.1 |
| Pathologic Complete Response (pCR) | 1 month after surgery | Pathologic Complete Response (pCR) after surgery |
| Renal Function Preservation | 3 month after surgery | Proportion of patients with ≤20% decline in eGFR at 3 months postoperatively |
| Safety and Tolerability | enrollment to 90 days after surgery | Incidence of Grade ≥3 treatment-related adverse events (CTCAE v5.0) |
Contacts
CONTACTjiwei huang
Outcome results
None listed